Is BGN p.Pro158Ser (c.472C>T) pathogenic?

BGN p.Pro158Ser (c.472C>T) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-29). AlphaMissense: likely pathogenic (0.9848); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Pro158Ser (c.472C>T)?

BGN p.Pro158Ser (c.472C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Pro158Ser (c.472C>T) in the general population?

BGN p.Pro158Ser (c.472C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BGN p.Pro158Ser (c.472C>T)?

AlphaMissense predicts likely pathogenic (score 0.9848) — an in-silico prediction, not a clinical call.

BGN p.Pro158Ser

c.472C>T · rs781803267 · VCV1742709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9848 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9848	likely pathogenic
REVEL	0.39	indeterminate
SaProt	LLR -10.49	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BGN
Protein: p.Pro158Ser
Coding: c.472C>T
MANE Select: NM_001711
dbSNP: rs781803267
Type: single nucleotide variant
Location: chrX:153505983 (GRCh38)
Structure: AlphaFold pLDDT 85.72

Full BGN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BGN p.Pro158Ala Uncertain significance ★★ ⚠ same residue
BGN p.Pro158Thr Uncertain significance ★ ⚠ same residue
BGN c.909+4A>G Uncertain significance ★★ same condition
BGN p.Ala330Asp Uncertain significance ★★ ⚠ same condition
BGN p.Ala330Pro Uncertain significance ★★ ⚠ same condition
BGN p.Ala41Ser Uncertain significance ★★ ⚠ same condition
BGN p.Ala44Thr Uncertain significance ★★ ⚠ same condition
BGN p.Arg106His Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bgn-p-pro158ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown